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Mitochondrial elongation in the macular RPE of aging monkeys, evidence of metabolic stress

  • Pathology
  • Published:
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Abstract

Purpose

This study was conducted to determine whether mitochondria of the macular retinal pigment epithelium (RPE) change with age in rhesus monkeys (Macaca mulatta). Mitochondria are the main instigators of oxidative stress, which has often been considered to play a role in the pathogenesis of age-related macular degeneration (AMD). Any pathological changes in the mitochondria of aging macular RPE, the main target of AMD, would be a clue to the pathogenesis of this common retinal degeneration afflicting both monkey and man.

Methods

Transmission electron microscopy was used to identify mitochondria and to determine their appearance, their density per unit area of RPE cytoplasm and their length. The eyes of seven monkeys, 1, 2, 6.5, 23, 26, 27 and 35 years of age, were studied. Measurements were kept separate for the basal, middle and apical third of each cell. The basal third of the macular RPE had many more mitochondria than the middle third, and the apical third was almost devoid of mitochondria.

Results

Mitochondrial number decreased and length increased with age. The increase in length was associated with an unusual clustering of mitochondria into parallel arrays of elongated mitochondria, with their long axis orthogonal to the basal membrane of the cell, structures not described before in RPE.

Conclusions

Mitochondrial elongation is associated with metabolic and/or oxidative stress, which implies that age produces stress in macular RPE. The increased clustering of very elongated mitochondria suggests that pathological changes occur in mitochondrial organization with age. These changes support the hypothesis that age-related mitochondrial dysfunction plays a role in the pathogenesis of AMD.

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Acknowledgments

We thank Krissty Brown for her assistance with electron microscopy, Julie Mattison from the National Institute on Aging for providing the elderly monkeys, and the Foundation Fighting Blindness and Research to Prevent Blindness, Inc., for their support. This work was also supported in part by NIH grants P51-OD011092 (MN), R01-EY015293 (PG), and P30-EY019007 (PG, TN) and a grant from the Eye Surgery Fund (TN).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Columbia University, New York City, NY, USA

    Peter Gouras & T. Nagasaki

  2. Edward S. Harkness Eye Institute, Research Annex, 635 West 165th Street, Box #76, New York, NY, 10032, USA

    Peter Gouras

  3. St. Erik’s Eye Hospital, Karolinska Institute, Stockholm, Sweden

    L. Ivert

  4. Oregon Health & Science University, Portland, OR, USA

    M. Neuringer

Authors
  1. Peter Gouras
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  2. L. Ivert
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  3. M. Neuringer
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  4. T. Nagasaki
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Corresponding author

Correspondence to Peter Gouras.

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Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; or expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures were approved by the Institutional Animal Care and Use Committee of the Oregon Health and Science University and the NIH primate center in Poolesville, Maryland, and conformed to the Guide for the Care and Use of Laboratory Animals (8th edition, 2011).

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Gouras, P., Ivert, L., Neuringer, M. et al. Mitochondrial elongation in the macular RPE of aging monkeys, evidence of metabolic stress. Graefes Arch Clin Exp Ophthalmol 254, 1221–1227 (2016). https://doi.org/10.1007/s00417-016-3342-x

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  • DOI: https://doi.org/10.1007/s00417-016-3342-x

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